Succinate dehydrogenase (SDH), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, has been identified as one of the most significant targets for pharmaceutical and agrochemical. Herein, with the aim of discovery of new antifungal lead structures, a class of novel N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were designed, synthesized and evaluated for their biological activities. They were bioassayed against seven phytopathogenic fungi, Rhizoctonia solani, Phytophthora infestans, Fusarium oxysporum f. sp. vasinfectum, Botryosphaeria dothidea, Gibberella zeae, Alternaria alternate and Fusarium oxysporum f. sp. niveum. The results indicated that most of the compounds displayed good antifungal activities, especially against R. solani. Among them, compounds 7 and 12 exhibited higher antifungal activities against R. solani in vitro with EC50 value of 0.034 mg/L and 0.021 mg/L, being superior to the commercially available fungicide bixafen (EC50 = 0.043 mg/L). Pot tests against R. solani showed that in vivo EC50 values of compounds 7 (2.694 mg/L) and 12 (2.331 mg/L) were higher than that of bixafen (3.724 mg/L). In addition, inhibitory activity of compound 12 against SDH indicated compound 12 (IC50 = 1.836 mg/L) showed good inhibitory activity against SDH, being close to bixafen's inhibitory activity (IC50 = 1.222 mg/L). And, molecular modeling of the SDH-compound 12 complex suggested that compound 12 could strongly bind to and interact with the binding site of the SDH. The results of the present work showed that N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were a new fungicides for discovery of SDH inhibitors and worth further study.

中文翻译：

---

发现 N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides 作为潜在的琥珀酸脱氢酶抑制剂

琥珀酸脱氢酶 (SDH) 是细胞呼吸链和三羧酸（或三羧酸）循环的重要组成部分，已被确定为制药和农用化学品最重要的目标之一。在此，为了发现新的抗真菌先导结构，设计、合成了一类新型 N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides 并评估了它们的生物活性。对它们进行了抗七种植物病原真菌、立枯丝核菌、致病疫霉、尖孢镰刀菌的生物测定。sp. vasinfectum、Botryosphaeria dothidea、Gibberella zeae、Alternaria alternaria 和 Fusarium oxysporum f。sp. 尼维姆。结果表明，大多数化合物表现出良好的抗真菌活性，尤其是对茄病菌的抗真菌活性。他们之中，化合物7和12在体外对R. solani表现出更高的抗真菌活性，EC50值为0.034 mg/L和0.021 mg/L，优于市售杀菌剂联苯吡菌胺（EC50 = 0.043 mg/L）。针对立枯病菌的盆栽试验表明，化合物 7 (2.694 mg/L) 和 12 (2.331 mg/L) 的体内 EC50 值高于联苯吡菌胺 (3.724 mg/L)。此外，化合物12对SDH的抑制活性表明化合物12（IC50=1.836mg/L）对SDH表现出良好的抑制活性，接近联苯吡菌胺的抑制活性（IC50=1.222mg/L）。并且，SDH-化合物12复合物的分子模型表明化合物12可以与SDH的结合位点强烈结合并相互作用。